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Details

Stereochemistry ACHIRAL
Molecular Formula C21H20N4O3
Molecular Weight 376.4085
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENTINOSTAT

SMILES

NC1=CC=CC=C1NC(=O)C2=CC=C(CNC(=O)OCC3=CN=CC=C3)C=C2

InChI

InChIKey=INVTYAOGFAGBOE-UHFFFAOYSA-N
InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26)

HIDE SMILES / InChI

Molecular Formula C21H20N4O3
Molecular Weight 376.4085
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17383217 https://www.ncbi.nlm.nih.gov/pubmed/21888556 https://www.ncbi.nlm.nih.gov/pubmed/12975486

Entinostat (MS-275) is an orally active, highly selective, small-molecule histone deacetylase inhibitor (HDACi) derived from benzamide. Entinostat preferentially inhibited HDAC1 versus HDAC3 and had no inhibitory activity toward HDAC8. The time to maximum plasma concentration (tmax) of entinostat ranged from 0.5 to 60h (median of 2h). Elimination of the drug was bi-exponential, with a terminal half-life of 30-80h. Entinostat is a well-tolerated that demonstrates promising therapeutic potential in both solid and hematologic malignancies. Its efficacy does not appear directly dose-related, and as such, more relevant biomarkers are needed to adequately assess its activity.

CNS Activity

Curator's Comment: Entinostat (MS-275) is a potent brain region-selective HDAC inhibitor in mice. https://www.ncbi.nlm.nih.gov/pubmed/16432198 Other study demostartes poor Entinostat (MS-275) brain penetration in non-human primates and rodents. https://www.ncbi.nlm.nih.gov/pubmed/20657706 No human data reported to date.

Originator

Curator's Comment: # Nihon Schering; Pfizer; University of Tokyo

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.3 µM [IC50]
8.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
45.1 ng/mL
10 mg/kg 1 times / 2 weeks multiple, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
114.3 ng/mL
4 mg/m² 1 times / week multiple, oral
dose: 4 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: Isotretinoin
ENTINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
529 ng × h/mL
10 mg/kg 1 times / 2 weeks multiple, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
586.6 ng × h/mL
4 mg/m² 1 times / week multiple, oral
dose: 4 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: Isotretinoin
ENTINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
51.6 h
10 mg/kg 1 times / 2 weeks multiple, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ENTINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
129.7 h
4 mg/m² 1 times / week multiple, oral
dose: 4 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: Isotretinoin
ENTINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
18.8%
10 mg/m² single, oral
dose: 10 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
ENTINOSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275.
2004 Jan 1
Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation.
2004 Sep 15
In vivo imaging of retinoic acid receptor beta2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cells.
2005 Jun 15
Ex vivo therapy of malignant melanomas transplanted into organotypic brain slice cultures using inhibitors of histone deacetylases.
2006 Aug
The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells.
2007 Mar
MAGE-A9 mRNA and protein expression in bladder cancer.
2007 May 15
Histone deacetylase inhibitors induce cell death and enhance the apoptosis-inducing activity of TRAIL in Ewing's sarcoma cells.
2007 Nov
Antiproliferative activities of a library of hybrids between indanones and HDAC inhibitor SAHA and MS-275 analogues.
2007 Nov 15
Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies.
2007 Sep 15
Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells.
2007 Sep 7
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.
2008 Jan 15
Histone deacetylase inhibitors in lymphoma and solid malignancies.
2008 Mar
Improved synthesis of histone deacetylase inhibitors (HDIs) (MS-275 and CI-994) and inhibitory effects of HDIs alone or in combination with RAMBAs or retinoids on growth of human LNCaP prostate cancer cells and tumor xenografts.
2008 Mar 15
Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells.
2008 May
Determination of a benzamide histone deacetylase inhibitor, MS-275, in human plasma by liquid chromatography with mass-spectrometric detection.
2009 Jan 15
Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL.
2009 Jul
Epigenetic modifiers: basic understanding and clinical development.
2009 Jun 15
Rescue of major histocompatibility-DR surface expression in retinoblastoma-defective, non-small cell lung carcinoma cells by the MS-275 histone deacetylase inhibitor.
2009 Mar
Epigenetic modulation of mGlu2 receptors by histone deacetylase inhibitors in the treatment of inflammatory pain.
2009 May
HDAC inhibitor SNDX-275 induces apoptosis in erbB2-overexpressing breast cancer cells via down-regulation of erbB3 expression.
2009 Nov 1
Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.
2009 Sep
Antidepressant actions of histone deacetylase inhibitors.
2009 Sep 16
MS275 enhances cytotoxicity induced by 5-fluorouracil in the colorectal cancer cells.
2010 Feb 10
Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275 and TSA on bladder cancer cells.
2010 Nov-Dec
Patents

Sample Use Guides

Phase I trial data have shown that daily dosing of entinostat is not tolerated. Administration of the drug every 2 weeks or weekly at doses of ≤10 mg/m2 was much better tolerated than daily dosing. The recommended phase II dose for entinostat is 4 mg/ m2 once weekly (solid tumors).
Route of Administration: Oral
Entinostat (MS-275) exerts dose-dependent effects in human leukemia cells, i.e., p21(CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations (e.g., 1 uM) and a marked induction of ROS, mitochondrial damage, caspase activation, and apoptosis at higher concentrations (e.g., 5 uM).
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:15:14 GMT 2025
Edited
by admin
on Mon Mar 31 18:15:14 GMT 2025
Record UNII
1ZNY4FKK9H
Record Status Validated (UNII)
Record Version
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Name Type Language
ENTINOSTAT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
MS-27-275
Preferred Name English
Entinostat [WHO-DD]
Common Name English
ENTINOSTAT [USAN]
Common Name English
Pyridin-3-ylmethyl ({4-[(2-aminophenyl)carbamoyl]phenyl}methyl)carbamate
Systematic Name English
CARBAMIC ACID, N-((4-(((2-AMINOPHENYL)AMINO)CARBONYL)PHENYL)METHYL)-, 3- PYRIDINYLMETHYL ESTER
Common Name English
entinostat [INN]
Common Name English
MS-275-27
Code English
ENTINOSTAT [JAN]
Common Name English
SNDX-275
Code English
Classification Tree Code System Code
EU-Orphan Drug EU/3/10/732
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
NCI_THESAURUS C1946
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
Code System Code Type Description
CAS
209783-80-2
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
PUBCHEM
4261
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
DRUG BANK
DB11841
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
WIKIPEDIA
ENTINOSTAT
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
SMS_ID
100000126009
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
EPA CompTox
DTXSID0041068
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
NCI_THESAURUS
C1863
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
CAS
442532-99-2
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
SUPERSEDED
INN
9016
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
USAN
TT-136
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
EVMPD
SUB33300
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
NSC
706995
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
ChEMBL
CHEMBL27759
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
FDA UNII
1ZNY4FKK9H
Created by admin on Mon Mar 31 18:15:14 GMT 2025 , Edited by admin on Mon Mar 31 18:15:14 GMT 2025
PRIMARY
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